Miyagishi R, Kikuchi S, Takayama C, Inoue Y, Tashiro K
Department of Neurology, Hokkaido University School of Medicine, Sapporo, Japan.
J Neuroimmunol. 1997 Jul;77(1):17-26. doi: 10.1016/s0165-5728(97)00040-4.
The chemokines RANTES, macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta are members of the beta-family of chemokines and potent chemoattractants for lymphocytes and monocytes. To investigate the factors which regulate lymphocyte traffic in experimental autoimmune encephalomyelitis (EAE), we studied, by in situ hybridization analysis, the kinetics of mRNA expression and the potent cellular sources of RANTES, MIP-1 alpha and MIP-1 beta in the central nervous system (CNS) during the course of EAE. RANTES-positive cells appeared in the subarachnoid space and infiltrated the subpial region at around day 10, increased to a peak at days 12-13 and then decreased following the resolution of the acute phase of EAE, though elevated RANTES message expressions still remained on chronic subclinical stage. Most of RANTES positive cells were identified as T-lymphocytes located mainly around blood vessels, by combined studies of in situ hybridization and immunohistochemistry. The remainder of the RANTES-positive cells were astrocytes and macrophages/microglia. MIP-1 alpha and MIP-1 beta mRNA-positive cells appeared around day 10, increased further on days 12-13 and then gradually decreased. Most of the MIP-1 alpha- and MIP-1 beta-positive mononuclear cells were located around blood vessels. The kinetics of RANTES, MIP-1 alpha and MIP-1 beta expression paralleled those of the recruitment of infiltrating inflammatory cells and disease severity. Our observations support the possibility that chemokine production by T-cells, macrophages and astrocytes lead to the infiltration of inflammatory cells into the CNS parenchyma during the acute phase of EAE.
趋化因子调节激活正常T细胞表达和分泌的趋化因子（RANTES）、巨噬细胞炎性蛋白（MIP）-1α和MIP-1β是趋化因子β家族的成员，是淋巴细胞和单核细胞的强效趋化剂。为了研究实验性自身免疫性脑脊髓炎（EAE）中调节淋巴细胞运输的因素，我们通过原位杂交分析，研究了EAE病程中中枢神经系统（CNS）中RANTES、MIP-1α和MIP-1β的mRNA表达动力学以及强效细胞来源。RANTES阳性细胞在第10天左右出现在蛛网膜下腔并浸润软脑膜下区域，在第12 - 13天增加到峰值，然后在EAE急性期消退后下降，尽管在慢性亚临床阶段RANTES信息表达仍保持升高。通过原位杂交和免疫组织化学的联合研究，大多数RANTES阳性细胞被鉴定为主要位于血管周围的T淋巴细胞。其余的RANTES阳性细胞是星形胶质细胞和巨噬细胞/小胶质细胞。MIP-1α和MIP-1β mRNA阳性细胞在第10天左右出现，在第12 - 13天进一步增加，然后逐渐减少。大多数MIP-1α和MIP-1β阳性单核细胞位于血管周围。RANTES、MIP-1α和MIP-1β表达的动力学与浸润性炎性细胞的募集和疾病严重程度的动力学平行。我们的观察结果支持了T细胞、巨噬细胞和星形胶质细胞产生趋化因子导致EAE急性期炎性细胞浸润到CNS实质中的可能性。
